Delhi govt should challenge ICMR with scientific evidence on plasma therapy’s efficacy in Covid-19, not with mere assertions
There is an ongoing debate over the efficacy of CPT in many jurisdictions.
Scientific rigour would treat all knowledge as pro tem till it is incontrovertibly established. Delhi health minister Satyendar Jain ought to have borne this in mind before he implicitly challenged the Indian Council of Medical Research’s (ICMR’s) position that convalescent plasma therapy (CPT) is not effective as a Covid-19 treatment line. The ICMR indicated on Tuesday that it would be removing the therapy from its Covid-19 treatment protocol; just a day after, Jain contended that CPT had shown significant efficacy in 2,000 patients in the national capital, including himself. The ICMR is basing its decision on the findings of its study that was put up on the pre-print server MedRxivt in September (now accepted for publication in BMJ); the study had found that CPT didn’t demonstrate any advantages on controlling disease severity and mortality reduction over the standard care protocol.
There is an ongoing debate over the efficacy of CPT in many jurisdictions. The ICMR study, termed the PLACID trial, was an open-label (patients knew what they were being administered, as opposed to the double-blind case), randomised controlled trial. Conducted in April-July with 464 subjects—235 receiving CPT and 229 receiving standard care—who had been hospitalised with ‘moderate’ Covid-19 severity, the trial found that there was no significant difference in the proportion of the subjects in the intervention (CPT) arm and the control (standard-care) arm in whom the disease didn’t progress to the severe stage over 28 days; apart from that, there was little difference in mortality (34 in the CPT arm versus 31 in the standard care arm).
While the structure of the ICMR study is more robust, in the sense that it tackles most biases that could creep in, some experts, as quoted in an article in The Print, believe that the wholesale inference that CPT is not effective overlooks a major limitation of the study—it didn’t measure the level of neutralising antibodies (NAbs) that are the most effective against any pathogen among all the antibodies that the pathogen triggers, in the plasma that was administered to the trial subjects.
This was because the technology to do this was not readily available in the country, a limitation that the ICMR study mentions, saying “A priori measurement of neutralizing antibody titres in donors and participants may further clarify the role of CP in management of COVID-19.” Those who recovered from a severe infection—largely belonging to high-risk groups such as the elderly, those with co-morbidities, etc—are most likely to have significant enough levels of NAbs in their plasm. Against the high likelihood of convalescent plasma donors being relatively young with a milder, even asymptomatic, manifestation of the disease, adequate NAb presence in plasma does become a confounding factor.
In the US, which gave emergency use authorisation (EUA) for the use of CPT in hospitalised patients, drugs regulator Food and Drugs Administration (FDA) had banked on observational studies, including one by Mayo Clinic involving 20,000 CPT subjects. The data suggested a ‘dose response’—mortality rate was the lowest among patients who had received the highest dose of antibodies through CPT and, conversely, was the highest among those who had received the lowest antibody concentrations.
To be sure, the US’s National Institutes of Health had advised caution just days after the FDA granted the EUA, saying that further evidence is required to conclusively draw up an informed stand for or against CPT’s efficacy. To that end, it has announced several grants for more rigorous studies.
There are still many uncertainties over Covid-19; against such a backdrop, sharply polarising stands sans scientific evidence don’t help. If the Delhi government has scientifically gathered and analysed data that can contradict the ICMR’s position on CPT, they should present these to counter the medical research authority. A summary statement such as Jain’s will only spark policy confusion and erode the trust among the masses.